OBJECTIVE: To examine the influence of cytokines on the release of soluble mediators in the peripheral blood and intrathecal compartments. RESULTS Cytokines, such as interleukin-1 (IL-1), are potent stimulators of endogenous cytokine release and the neuroendocrine axis, and thus play an important role in the communication between the immune system and the brain. We have been investigating the influence of IL-1 on other cytokines, such as interleukin-6, in the peripheral blood and intrathecal compartments. Following our demonstration that IL-6 is released endogenously from within the CNS, we have been investigating the primary cellular source. In addition, we have been investigating the degree to which corticosteroids are involved in modulating the proinflammatory responses, which has bearing on the use of steroids in the treatment of sepsis and anaphylactic shock. FUTURE DIRECTIONS Our studies are now focused on endothelial cells of the blood-brain-barrier. For this project, we have established endothelial cell cultures that will permit the research to go forward with in vitro modelling of the BBB. KEY WORDS cytokines, interleukin-1, interleukin-6 cerebrospinal fluid, psychoneuroimmunology NSF Predoctoral fellowship, NIMH MH41659